Methods for treating metabolic disorders using FGF

Abstract

The method provides methods and compositions for treating metabolic disorders such as impaired glucose tolerance, elevated blood glucose, insulin resistance, dyslipidemia, obesity, and fatty liver.

What is claimed is: 
     
       1. A method for treating a diabetic, hyperglycemic, and/or insulin resistant individual who has a body mass index (BMI) of 25 or higher, comprising administering a functional fragment of FGF-1 comprising at least 80% of human FGF-1 and at least one variation at an amino acid residue position selected from K112, K113, K118, R122, or K128 to the individual in an amount effective to reduce body fat in the individual and/or increase lean muscle mass in the individual. 
     
     
       2. The method of  claim 1 , wherein the functional fragment of FGF-1 is administered intravenously. 
     
     
       3. The method of  claim 1 , wherein the functional fragment of FGF-1 is administered subcutaneously. 
     
     
       4. The method of  claim 1 , wherein the functional fragment of FGF-1 is administered at a dose of 0.01-1 mg FGF-1 per kg body weight. 
     
     
       5. The method of  claim 1 , wherein the functional fragment of FGF-1 is administered once per day. 
     
     
       6. The method of  claim 1 , wherein the functional fragment of FGF-1 is administered in combination with an additional therapeutic compound. 
     
     
       7. The method of  claim 6 , wherein the additional therapeutic compound is an alpha-glucosidase inhibitor, amylin agonist, dipeptidyl-peptidase 4 (DPP-4) inhibitor, meglitinide, sulfonylurea, or a peroxisome proliferator-activated receptor (PPAR)-gamma agonist. 
     
     
       8. The method of  claim 7 , wherein the PPAR-gamma agonist is a thiazolidinedione (TZD), aleglitazar, farglitazar, muraglitazar, or tesaglitazar. 
     
     
       9. The method of  claim 8 , wherein the TZD is pioglitazone, rosiglitazone, rivoglitazone, or troglitazone. 
     
     
       10. The method of  claim 1 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 80% sequence identity to amino acids 1-140, amino acids 1-141, amino acids 14-135, or amino acids 13-135 of FGF1. 
     
     
       11. The method of  claim 1 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 80% sequence identity to amino acids 14-135 of FGF-1. 
     
     
       12. The method of  claim 1 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 90% sequence identity to amino acids 1-141 of FGF-1. 
     
     
       13. The method of  claim 1 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 95% sequence identity to amino acids 1-141 of FGF-1. 
     
     
       14. The method of  claim 1  wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 98% sequence identity to amino acids 1-141 of FGF-1. 
     
     
       15. The method of  claim 1 , wherein the functional fragment of FGF- 1  is administered daily, twice daily, every other day, bi-weekly, weekly, or monthly. 
     
     
       16. The method of  claim 1 , wherein the individual has a BMI of greater than 30. 
     
     
       17. The method of  claim 1 , wherein the individual has a BMI of 35 to 40. 
     
     
       18. The method of  claim 1 , wherein the at least one variation is a conservative variation. 
     
     
       19. A method for treating a diabetic, hyperglycemic, and/or insulin resistant individual who has a fatty liver disease, comprising administering a functional fragment of FGF-1 comprising at least 80% of human FGF-1 and at least one variation at an amino acid residue position selected from K112, K113, K118, R122, or K128 to the individual in an amount effective to reduce liver steatosis. 
     
     
       20. The method of  claim 19 , wherein the fatty liver disease is nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), or simple fatty liver (steatosis). 
     
     
       21. A method for treating an individual having type II diabetes or who is insulin resistant, comprising administering a functional fragment of FGF-1 comprising at least 80% of human FGF-1 and at least one variation at an amino acid residue position selected from K112, K113, K118, R122, or K128 to the individual in an amount effective to reduce blood glucose levels.